This invention relates to cell electrical stimulators and reading probes for animals, including humans, in general, and brain electrical stimulators and reading probes in particular.
It is well established that the neuron signals are electrical propagating signals. The roots of this fact can be traced at least to the Italian Luigi Galvani as early as 1771 with his famous frog's leg experiment. Electrically stimulating neurons that carry orders to muscles, or electrically stimulating the muscles directly, can therefore cause the muscles to contract or relax. It follows that the spinal cord and the whole brain, being as they are a collection of neurons, are electrical devices, the function of which could be expected to be affected if electrical currents were forced on them by some external agent.
Focusing attention now on the brain, it has been established that different brain functions occur in different parts of it, though some parts of the brain are known to be shared by more than one function. The French Paul Broca is credited with the first unequivocal evidence that the brain is segmented in areas with specialized functions (brain workers say “area” for what is actually a volume, a particular three dimensional part of the brain, practice that I will follow here, occasionally calling the attention of the reader to this misuse of the word). Paul Broca proved that speech is processed and controlled at a small area (that is, a volume) today known as the “Broca area” which is located in the left frontal lobe. Today the parts of the brain that are associated with speech, or with vision, or with the motion of the hand or with the motion of the big toe on the left foot, an so on, are all known; the brain is all mapped, as known in the trade. Eric R. Kandel (Eric R. Kandel, James H. Schwartz, and Thomas M. Jessell “Principles of Neural Science” 4th edition (2000)) gives a good overview of the current state of the art from the academic point-of-view.
It follows from these two facts that electrical stimulation of any particular area of the brain (that is, a volume) should affect the function that depends on this area: speech, vision, motor, etc. This was indeed experimentally determined to be true, and eventually brain electrical stimulators were developed to affect parts that became dysfunctional. Brain stimulation to correct for motor disorders is the most common clinical application today, but stimulation can also cause emotions when it happens in the area that is associated with them. Similarly, stimulation of nerves that carry information from the body to be brain can stop (or cause) pain, and electrically stimulating the heart can keep it at the correct pace, or even to restart it when it happens to stop, as is done with pacemakers and defribilators. Electrically stimulating neurons that carry orders to muscles, or electrically stimulating the muscles directly, can therefore cause the muscles to contract or relax. This is what is achieved with heart pacemakers and heart defibrillators. A pacemaker could, in principle work stimulating the part of the brain that starts the process (assuming it is not autonomous), but this would be more complicated than stimulating the heart directly, so pacemakers are designed to affect the heart directly, and not the origin of the signal.
Leaving aside the mechanisms that underlie the result of electrical stimulation, which are not well known in all cases, it is possible today to use direct electrical stimulators to modify motor malfunctions as Parkinson's disease, essential tremor or epilepsy, or mood states as depression, or complex syndromes as eating disorders. Said brain electrical stimulation is achieved with electrodes permanently implanted in the desired part of the brain, which are connected to the necessary electrical power source (batteries or the like) and electronic circuitry to generate the appropriate electrical pulse. Severe diseases as Parkinson's disease are now treatable and often totally or largely curable, or at least substantially controlled, with direct electrical stimulation to the appropriate part of the brain. For Parkinson's disease stimulation, the device is one of a class generally known as Deep Brain Stimulators (DBS), because all the known parts of the brain that receive electrical stimulation to counter Parkinson's disease are located deep inside it, as the thalamus, the subthalamic nucleus (STN), the basal ganglia, or internal globus pallidus (GPi) the internal capsule and the nucleus accumbens. The electrical pulse for DBS is AC (alternate current) at f=˜180 Hz (or 5.56 milliseconds between pulses), each pulse lasting approximately 90 microseconds (pulsewidth). The voltage depends on the patient, varying from as low as 2.5 V to as high as 5 V (all values approximate, varying between patients and also with time on the same patient). A separate class of stimulators are the superficial brain stimulators, known as cortical stimulators, that stimulate the brain cortex, which could also use the invention disclosed in this patent application with appropriate adaptations, largely on the geometry of the stimultor. There are also spinal stimulators, that stimulate the nerves at the spinal column, and other parts of the body, generally for pain control, but also for other problems. There are heart stimulators or pacemakers and also heart defribilators. These latter, heart pacemakers and defribilators, differ much from the device disclosed as the main embodiment of this patent application, but the same core principle disclosed in this invention, the method and means of more precisely applying the stimulation, and of shaping the electric field, so as to guide the current, apply to them too. Another application is artificial muscle stimulation, where artificial materials capable of contraction or distention when receiving the appropriate signal are used as artificial muscles. Another class of devices is composed of measuring probes, designed to measure the voltage (or current) in the brain or other body parts. All these variations can incorporate the system and method disclosed here to allow the use of a very large number of electrical contacts for stimulation or for measurement.
The success of DBS to ameliorate Parkinson's disease symptoms is known in the medical community, particularly among neurosurgeons. Yet, many forms of Parkinson's diseases and other movement disorders too, are either unresponsive or only partially ameliorated by DBS (Michael S. Okun et al. “Multiple lead method for deep brain stimulation” A61N 1/00 International Application No.: PCT/US2005/033730 University of Florida Research Foundation, Inc.—30 Mar. 2006). It is unknown the causes of the differences, but one of the speculations is not optimal positioning of the stimulating electrode, which would, as expected, fail to have optimal effect in this case due to failure to stimulate the chosen area. Benabid (1994) (A. L. Benabid, et al., Stereofact Funct Neumsurg., 62(1-4):76-84 (1994)) and Benabid (2001) (A. L. Benabid, et al. J Neurol., 248 Suppl 3: 11137-47 (2001)) discuss this problem and others. Additionally, the success of DBS procedures can diminish over time. This deleterious effect is discussed by M. C. Kim et al. (M. C. Kim, B C Son, Y Miyagi, J- K Kang, “Vim thalamotomy for Holmes' tremor secondary to midbrain tumour”J Neurol Neurosurg Psychiatry, 73:453-455 (2002)). This latter decrease in efficacy of DBS is thought by some neurosurgeons to arise from motion of the implant inside the brain due to occasional sudden head movements, particularly due to a falling but also other causes. Our invention allow for correction of these deleterious factors.
Known side effects from brain stimulators caused it to be recognized the need for smaller electrode area for neural stimulation, but since nobody has been able to precisely position the stimulator in the brain, the only option has been to stimulate an area that is likely to be larger than necessary. This has been a widely known problem in the art of brain stimulators: unwanted side effects, as mood changes, uncontrolled motion of other muscles not intended to be affected, etc.
In “Detailed description”, section A-1 Andrew Firlik et al. (Andrew Firlik et al. “Methods and apparatus for effectuating a lasting change in a neural-function of a patient” U.S. Pat. No. 7,577,481 (Aug. 18, 2009)) states that “The method 100 includes a diagnostic procedure 102 involving identifying a stimulation site at a location of the brain where an intended neural activity related to the neural-function is present.”, which indicates that these inventors are aware of the need to identify a location of the brain where to apply stimulation. Yet their device assumes that the implant is indeed positioned at the desired target location, which the neurosurgeons know to be a very difficult task. Indeed, the difficulty of this task is indicated by the acceptance by the neurosurgeon community of the side effects, which arises from incorrect positioning of the stimulating device, which then applies electrical current also into undesired areas, thereby causing the known side effects. Our device offers a great latitude of the electrical stimulation point, thereby solving this problem. Moreover, Firlik et al. (U.S. Pat. No. 7,577,481) disclose an innovative application of their invention, which is to use electrical stimulation during physical therapy designed to readapt the brain of patients that have suffered some form of brain loss, either from a stroke, a car accident or the like. Such an application would require an adjustment of the stimulation site, which is difficult to achieve with the device they disclose, while the device we disclose in our invention is more suitable for readjusting the point of application of the electrical stimulation.
Wiler at al. (Allen Wyler and Brad Fowler, “Systems and methods for selecting stimulation sites and applying treatment, including treatment of symptoms of Parkinson's disease, other movement disorders, and/or drug side effects” U.S. Pat. No. 7,565,200 (Jul. 21, 2009)) At the end of the background section, the inventors acknowledge that: “Because MCS involves the application of stimulation signals to surface regions of the brain rather than deep neural structures, electrode implantation procedures for MCS are significantly less invasive and time consuming than those for DBS. As a result, MCS may be a safer and simpler alternative to DBS for treating PD symptoms. Present MCS techniques, however, fail to address or adequately consider a variety of factors that may enhance or optimize the extent to which a patient experiences short term and/or long term relief from PD symptoms.” Which is likely to be a consequence that their invention is unable to precisely adjust the point of application of electrical stimulation, which is exactly the solution proposed by our invention. It is apparent, therefore, that the need for precisely pinpointing the location of application of the electrical stimulation is known in the art, at the same time that its solution has evaded solution.
Anne Pianca (Anne Pianca, “System for permanent electrode placement utilizing microelectrode recording methods” U.S. Pat. No. 7,177,701 (Feb. 13, 2007)) discloses a DBS system that works in association with a separate measuring electrode which aids in the location of the optimal placement of the DBS device. Yet Pianca's invention suffers from the disadvantage of increased trauma to the patient due to multiple insertions and withdraws of invasive instruments in the brain. A better solution would avoid such traumatic repetitive insertions. Our invention provide such improvement.
Benjamin Pless (Benjamin Pless et al. “Seizure sensing and detection using an implantable device”, U.S. Pat. No. 6,810,285, (Oct. 26, 2004)) also describes a device that reads the waveforms produced by the brain, similarly to a EKG, and acts on these measurements, under the control of a microcomputer or similar device, to inject electrical current in the brain to forestall such symptoms as epileptic seizures. Pless device again fails to teach any means to precisely measure and to precisely insert the electrical corrective pulse.
Potential movement of the device, as well as other characteristics, are also disclosed in another US patent by Carl Wahlstrand (Carl Wahlstrand et al. “Reducing relative intermodule motion in a modular implantable medical device”, U.S. Pat. No. 7,392,089 (Jun. 24, 2008)), but again these inventors fail to solve the problem of the number of electrodes and the possible number of wires to use.
Brain stimulation is known to have other effects besides motor in nature. For example, R. Hu (R. Hu, E. Eskandar, Z. Williams, “Role of deep brain stimulation in modulating memory formation and recall” Neumsurg Focus. 2009 July; 27 (1):E3), discuss the effects of it in memory formation. Hu's work is an indication of the possible side effects that may occur if the brain stimulation, intended to stimulate a certain part of it, goes beyond the intended area.
A good analysis of the pros and cons of the use of direct electrical brain stimulation can be found in B. Kluger et al., (B. M. Kluger, O. Klepitskaya, M. S. Okun, “Surgical treatment of movement disorders” Neurol Clin. 2009 August; 27(3): 633-77, v. Review).
Finally, there is the problem of DBS in children, whose brains are guaranteed to change size, thereby invalidating the initial positioning of the implant. W. Marks (W. A. Marks, J. Honeycutt, F. Acosta, and M. Reed “Deep brain stimulation for pediatric movement disorders” Semin Pediatr Neurol. 2009 June; 16(2): 90-8. Review), review the use of DBS in children. This is a particular interesting and valuable application of our device because as children grow, the distal extremity of the implant slides away from its initially implanted location. With our device, with its larger number of electrodes, there exists a larger latitude of reprogramming to continue stimulating the same area (volume) of the brain after it slipped away due to growth.
Brain electrical stimulation is made with an electrode capable of delivering electric current to a chosen area (volume) of the brain. There exist two general classes of brain stimulators: cortical and deep brain stimulators. In a later section I will describe a preferred embodiment of my invention for deep brain stimulation, and accordingly I will describe here a current art used for deep brain stimulation. Cortical brain stimulators, spinal (nerve) stimulators, etc., function on substantially similar principles, as known to the people familiar with the art, the adaptations for which are obvious to the ones familiar with the art. Similar adaptations of the invention disclosed below are also, mutatis mutandis, used for measurement devices, that is, for electrodes designed to measure the electrical activity inside body cavities, particularly at the neurons. Similar adaptations of the invention disclosed herein are also possible for cardiac stimulators, for example. Cardiac stimulators can also improve with more precise location of the electrical stimulating pulses, as provided by our invention.
A DBS (Deep Brain Stimulator) is an electrical stimulator device composed of a battery for electrical power, an electronic circuitry for electrical pulse generation of appropriate amplitude, frequency, pulse width and shape, connecting wires and a wand, or lead, or picafina, from now on referred to as the picafina, that delivers an electrical pulse to the brain target location (we call the device of our invention “picafina”, which is a supporting structure used by the main embodiment of our invention, generally similar to the devices used in Deep Brain Stimulation but potentially with far more tips or electrodes than DBS devices, which is strong enough to allow it to be inserted in the brain or other body structures, and which contains the necessary wires for connecting the measuring tips and the address decoders with the controlling and measuring instruments. For use in human animals, he dimension of a type I picafina is approximately the diameter of a wide drinking straw (5 mm.), its length being the necessary to reach the desired depth in the body. For smaller animals (as a mouse), the picafinas would be accordingly smaller, both in diameter and length, while for larger animals (as a whale or an elephant), the picafinas would be accordingly larger.) The battery and microelectronic circuitry are housed in a hermetic sealed housing of material compatible with human tissue. This housing is typically implanted under the clavicle or somewhere else in the chest, from where extension wires are passed under the skin up the neck, usually behind the ear, to bring the electrical pulse from the generating box to the picafina. Alternatively the programmable oscillator and battery are located on the patient's skull, as disclosed by Pless et al., U.S. Pat. No. 6,810,285, or by Janzig et al. “Low Profile Implantable Medical Device” International Application No.: PCT/US2003/038927, but the physical location of the electronic circuit and battery are of no importance for the functioning of the device disclosed in this invention. For DBS, the picafina is inserted from a burr hole on the top of the skull, vertically down, deep within the brain, to deliver the electrical pulses at some appropriate target area. The picafina, which is the only part inside the brain, has the approximate dimension of a 3 in. long drinking straw: 7 cm long, 3 to 5 mm diameter. At the picafina's distal end there are typically four metallic rings, each one individually connected by an independent wire that runs inside said picafina to the proximal end of it, then, via extension wires to the electrical pulse generator usually implanted in the patient's chest. Each metallic ring is able to originate an electric pulse of a few volts, 90 microseconds pulsewidth, 180 Hz frequency (that is, 5.55 milliseconds between pulses), all typical values, varying from patient to patient, also varying with time on the same patient. The pulsewidth and frequency are usually the same for all patients, while the voltage depends on the patient, as well as which rings are connected. It is conjectured that the required variations in the applied electric potential (voltage) are consequence of changes in impedance perhaps caused by deposits on the ring-shaped electrodes, but the reasons for this do not impact our invention. Examples of current art picafinas can be seen at the web reference Medtronic (2009).
Dennis D. Elsberry, Mark Rise and Gary King (Dennis D. Elsberry, Mark Rise and Gary King, “Method of treating movement disorders by brain stimulation and drug infusion” U.S. Pat. No. 6,094,598 (Jul. 25, 2000)) disclosed in 2000 a device that relies on both drug and electrical current delivery to affected areas of the brain, as a control to motion disorders, as our invention does. Their device lacks the flexibility of choice of electrical initiation point that our device has. Our device is only electrical, not chemical though, as are the majority of current DBS (Deep Brain Stimulation).
The multiplicity of contacts also serve to adjust the exact point at which the electrical current is injected into the brain, because it is known to be difficult for the neurosurgeon to position said picafina on a target area that the neurosurgeon cannot see inside the brain, with precision better than a few millimeters away from the desired location. Ultimate current injection location is adjusted by selecting one or other (or several) of said contacts. Ring selection, and voltage selection as well, are made after surgery, in what is known as programming sessions, during which information is send by telemetry (radio waves, magnetic links, or their equivalents), during which the device is adjusted for the particular needs of the patient.
Current art suffers from many problems, some of which are as follows. If the electrical contacts are circular rings, the current is injected 360° around the picafina, approximately the same amount in all directions, and reaching the same distance from the picafina on all directions. Therefore current art does not solve the problem of directionality, apparently because nobody has been able to have a large number of point-like smaller electrical contacts all over the picafina, and capable of being independently turned on or off as needed. This lack of directionality is not good because the picafina is seldom positioned at the dead center of the target location—the surgeon cannot see inside the brain as he/she inserts the picafina, and the regions look the same anyway, so even if the surgeon were able to see the region near the picafina when it is inserted, it would make little difference for its positioning. The surgeon can, and indeed does, apply current as he/she inserts the device, then ask the patient, who is awake during surgery, what he/she feels or thinks, which feelings and thoughts are influenced by the electrical input, from which the surgeon can determine where the picafina is at that moment. Successive observations, during surgery, of the effects of electric stimulation as the neurosurgeon inserts deeper the device allows him/her to eventually find the target location—but hardly the dead center of the target location. Indeed, though the relative position of all brain structures is substantially the same on all patients, their physical sizes, and therefore their absolute position with respect to any fiducial mark, say, the picafina's entrance hole on the skull, is not the same. This is true for internal as well as external features: all humans have their noses above their mouths but their absolute distances measured from, say, the forehead, vary from individual to individual. It follows that the electrode positioning is less accurate than desirable. Exact position of the picafina is also difficult because of the target regions are usually small, of the order of a few mm only. This imprecision in positioning causes then that either the current will not spread through the whole volume of interest, or else will spread outside it (see FIGS. 10a and 10b). Neither is satisfactory, because when the electrical current does not perfuse the target area there is under-treatment, while when the current invades nearby areas there may occur side effects due to stimulations of areas that are not intended to be stimulated. Neither is good for the patient. Both cases are known to exist, and because no solution has been found to control the injected electric current to different distances toward different directions, neurologists just accept them as fact-of-life. If the picafina is of a newer type, already in the market, with square or circular pads, the current can be injected in one or more directions, as needed, but with insufficient positional control, also not ideal for the patient. The inventors know of a Medtronic Inc. (710 Medtronic Parkway/Minneapolis, Minn. 55432-5604) picafina with 12 small pads of approximately 1 mm diameter, which is insufficient in number to precisely direct the injected current towards a preferred direction. It appears that Medtronic is trying to solve the directional problem but have been unable to add more pads, most likely due to lack of space for individual wires inside the picafina. Indeed, the very introduction of the few individual electrical contacts indicate that the need for many controllable points is known, though the solution has been eluding the practitioners of the art. Our invention solves this problem of controlling a large number of electrical pads, a known problem which solution have been eluding the practitioners of the art.
It stands to reason that in all cases when the inserting rod is close to the edge of the target region, shooting the current in all directions is not desirable, as the current will enter in areas that would be better left alone, as they are functioning normally. Indeed, DBS side effects are known to occur, which can be of a motor nature, as facial pulling, etc. but also of a mood or personality nature, including increased/decreased aggressiveness, depression/elation, etc. It is therefore desirable to have a means and a method to direct the electrical current into some specific direction only, starting from the imperfect positioning of the picafina, a problem that is not addressed by exiting DBS devices.
Analyzing the disclosed inventions and products in the market, it seems that the practitioners of the art are all aware of the desirability of having available the possibility of precisely controlling the point of insertion of the stimulating current in the brain (or heart, or spinal column, or etc.), for which only the obvious solution has been tried, which is to precisely position the stimulating electrode in the target region. Another possibility was never investigated, which is to implant a large number of small electrodes in the general vicinity of the target area, followed by the selection of the correct initiation point out of the large number of them. It seems that the last possible solution have not been tried because of the large number of wires necessary to connect each pad or contact to the electric power and electronics circuitry outside of the inserted electrode.
Other details on the current art picafina are known to the ones skilled in the art, while still others are unknown manufacturers' trade secret.